Hormone Replacement Therapy for Vasomotor Symptoms with Intact Uterus
For a postmenopausal woman with vasomotor symptoms and an intact uterus, prescribe combined estrogen plus progestin therapy at the lowest effective dose for the shortest duration necessary to control symptoms. 1, 2
Mandatory Combination Therapy
Women with an intact uterus must receive progestin in combination with estrogen to prevent endometrial cancer. Unopposed estrogen is contraindicated as it significantly increases endometrial cancer risk 3, 1, 2, 4
The strongest evidence for endometrial protection comes from oral cyclical combined treatment, though micronized natural progesterone may offer some advantages 3
Alternative option: Estrogen combined with bazedoxifene (a selective estrogen receptor modulator) can be used instead of progestin for women who cannot tolerate progestogen side effects 5, 4
Recommended Estrogen Formulations and Dosing
17-beta estradiol is preferred over ethinylestradiol or conjugated equine estrogens for estrogen replacement 3
Start with the lowest effective dose: conjugated estrogens 0.3 mg, 0.45 mg, or 0.625 mg daily have all demonstrated statistically significant efficacy for vasomotor symptoms compared to placebo 2
Lower doses (0.3 mg conjugated estrogens or estradiol 0.25 mg/day) are equally effective at relieving vasomotor symptoms with fewer adverse events and better patient continuation rates 6
Route of Administration Considerations
Transdermal estradiol may have lower cardiovascular and venous thromboembolism risk compared to oral formulations, particularly in women with hypertension or prothrombotic risk factors 3, 7
However, oral formulations have demonstrated clinical benefits in relieving vasomotor symptoms and preventing osteoporosis 8
Patient preference for route and method of administration must be considered when prescribing 3
Treatment Duration and Monitoring
Use HRT only for symptom management, not for chronic disease prevention. The U.S. Preventive Services Task Force gives a Grade D recommendation against routine use for prevention due to harmful effects (increased breast cancer, stroke, venous thromboembolism, coronary heart disease) outweighing benefits 3, 1
Prescribe for the shortest duration consistent with treatment goals—risks increase with duration beyond 5 years 3, 1
Reevaluate patients periodically at 3-6 month intervals to determine if treatment is still necessary 2
Risk-Benefit Quantification
For 10,000 women aged 50-79 taking estrogen-progestin for 1 year: expect 7 additional coronary heart disease events, 8 more strokes, 8 more pulmonary emboli, and 8 more invasive breast cancers, but 6 fewer colorectal cancers and 5 fewer hip fractures 3, 1
The benefit-risk balance is most favorable for women ≤60 years old or within 10 years of menopause onset with severe vasomotor symptoms 3
Absolute Contraindications
- History of breast cancer 3, 1
- Coronary heart disease 3
- Previous venous thromboembolic event or stroke 3
- Active liver disease 3
- Antiphospholipid antibody syndrome or thrombotic APS 3
Common Pitfalls to Avoid
Never prescribe unopposed estrogen in women with an intact uterus—this is the most critical error that leads to endometrial cancer 3, 1, 2
Do not use HRT for cardiovascular disease prevention—evidence shows increased coronary heart disease risk, not benefit 1
Avoid prescribing HRT for chronic disease prevention rather than symptom management—the harms outweigh benefits for this indication 3, 1
Do not continue therapy indefinitely without reassessment—use the minimum duration necessary 3, 1, 2